Why Alendronate Can Be Taken for a Short Time
Alendronate is designed for short-term use (typically 5 years) because bisphosphonates incorporate into bone matrix and continue to suppress bone resorption even after discontinuation, while prolonged use beyond 5 years increases the risk of rare but serious adverse events like atypical femoral fractures and osteonecrosis of the jaw without providing additional fracture protection for most patients. 1, 2
Mechanism Explaining Short-Term Efficacy
Alendronate binds permanently to bone hydroxyapatite at sites of active bone remodeling, where it remains incorporated within the bone matrix and continues to inhibit osteoclast activity even after you stop taking the medication 2
The drug's residual effect persists because bone remodeling is a slow process—alendronate deposited in bone during treatment continues to be released and exert anti-resorptive effects as that bone is gradually remodeled over subsequent years 2, 3
Studies show that normal bone forms on top of alendronate-containing bone, and while the incorporated drug is not pharmacologically active in the matrix, it becomes active again when that bone undergoes remodeling 2
Evidence-Based Treatment Duration
The FDA label and American College of Physicians both specify that the optimal duration has not been determined, but standard treatment is 5 years, with all patients requiring periodic reassessment of fracture risk 4, 2
The FLEX trial demonstrated that women who discontinued alendronate after 5 years had only a modest increase in clinical vertebral fractures (5.3% vs 2.4%) but no difference in non-vertebral or hip fractures over the subsequent 5 years, indicating that most patients retain substantial fracture protection during a drug holiday 1, 3
Extending treatment beyond 5 years probably reduces vertebral fractures but does NOT reduce hip or other non-vertebral fractures, while increasing the risk of long-term adverse events 1, 5
Risk-Benefit Analysis Supporting Short Duration
Increasing Risks with Prolonged Use
Atypical femoral fractures increase from 1.78 per 100,000 person-years to 113 per 100,000 person-years with exposure greater than 8 years, representing a 63-fold increase in risk 1
Osteonecrosis of the jaw incidence is very rare at <1 case per 100,000 person-years with standard osteoporosis dosing, but risk increases significantly with duration beyond 5 years 1, 5
Asian patients face up to 8 times higher risk for atypical femoral fractures than White patients (595 versus 109 per 100,000 person-years), making duration considerations even more critical in this population 1
Sustained Benefits After Discontinuation
Bone mineral density gains achieved during the first 5 years are largely maintained during drug holidays of 2-3 years, as the incorporated bisphosphonate continues to suppress bone resorption 1, 3
The American College of Physicians recommends NOT performing routine BMD monitoring during the initial 5-year treatment period, as fracture reduction occurs even without BMD increases, emphasizing that the drug's effect is not dependent on continuous administration 1, 5
Clinical Decision Algorithm After 5 Years
Patients Who Should STOP Treatment (Drug Holiday)
- No hip or vertebral fractures during the 5-year treatment period 1, 5
- Hip BMD T-score > -2.5 after treatment 1, 5
- Age < 70 years without multiple risk factors 1
- No ongoing high-dose glucocorticoid use (≥7.5 mg prednisone daily) 1, 5
Patients Who Should CONTINUE Beyond 5 Years
- Previous hip or vertebral fracture (especially if occurring during treatment) 1, 5
- Hip BMD T-score ≤ -2.5 despite 5 years of treatment 1, 5
- Age ≥ 80 years 1, 5
- Multiple non-spine fractures 1, 5
- Ongoing glucocorticoid use ≥ 7.5 mg prednisone daily 1, 5
Critical Pitfalls to Avoid
Do not automatically continue bisphosphonates beyond 5 years without reassessing fracture risk, as this exposes patients to unnecessary rare adverse events without proven additional benefit in low-risk individuals 1
Ensure dental work is completed before initiating or continuing bisphosphonate therapy to reduce osteonecrosis of the jaw risk, particularly important when considering treatment beyond 5 years 1, 5
Never confuse alendronate's drug holiday strategy with denosumab—denosumab drug holidays are NOT recommended due to risk of rebound fractures, and if discontinued, bisphosphonate therapy must be initiated within 6 months 1, 5
During a drug holiday, reassess patients regularly for new fractures, changes in fracture risk profile, and consider resuming therapy if a new fracture occurs or fracture risk increases significantly 1